The Effect of Prostaglandin Synthetase Inhibitors on Human Preovulatory Follicular Fluid Prostaglandin, Thromboxane, and Leukotriene Concentrations*

Abstract

This study evaluates the eicosanoid concentration in luteinized unruptured follicles (LUFs) on the ovaries of patients who had been treated with inhibitors of prostaglandin synthetase. Indomethacin, bromfenac, or azapropazone (or a placebo) was administered orally to 41 women during the periovulatory period. Follicular development was monitored by serial ultrasound examinations, and the onset of ovulation was regulated by an injection of hCG. Follicular fluid was aspirated during sterilization by minilaparotomy, which was performed just before the expected time of ovulation. Prostaglandin E2 and PGF2 alpha levels in the fluid were significantly reduced by indomethacin and bromfenac compared to those after placebo treatment. Bromfenac also reduced the follicular fluid leukotriene B4 level. Therefore, the development of luteinized unruptured follicles after treatment with nonsteroidal antiinflammatory drugs appears to be associated with a significant decrease in the synthesis of ovarian eicosanoids.

The mare as a model for luteinized unruptured follicle syndrome: intrafollicular endocrine milieu

“…Intrafollicular PGF 2 a, PGFM, and PGE 2 were consistently decreased in mares of the induced LUF group. Similar results have been shown in the follicular fluid of women treated with various NSAIDs (Priddy et al 1990). Prostaglandins are vital for the ovulatory process in vertebrates (reviewed in Murdoch et al (1993)).…”

“…Likewise, higher plasma E2 concentrations have been described in women with spontaneous LUFs (Hamilton et al 1985). However, no differences in intrafollicular E2 concentrations were previously documented in women following NSAID treatment (Priddy et al 1990). Estradiol-mediated stimulation of PGE 2 synthesis in preovulatory follicles in mice (Toda et al 2012) may explain the increased PGE 2 :PGF 2 a ratio in mares of the induced LUF group.…”

“…The ultrasonographic morphological characteristics of naturally occurring or induced LUFs are similar in women (Priddy et al 1990, Zaidi et al 1995 and mares (Coetsier & Dhont 1996, Cuervo-Arango & Newcombe 2012. LUF formation involves the development of well-vascularized luteal tissue, as indicated by echotexture and color Doppler signals in both women and mares (Zaidi et al 1995, Ginther et al 2007a.…”

“…Use of pharmacological agents in fertility or superovulatory treatments has increased the occurrence of LUFs and/or anovulatory follicles in women (Martinez et al 1991, Ghanem et al 2009) and mares (Lefranc & Allen 2003, Ginther et al 2008a, CuervoArango & Newcombe 2010, Meyers-Brown et al 2011. Similarly, intrafollicular or systemic administration of prostaglandin inhibitors has been shown to cause luteinization of follicles in rats (Armstrong & Grinwich 1972), rabbits (Salhab et al 2003), mares (Watson & Sertich 1991, Cuervo-Arango & Domingo-Ortiz 2011, and women (Killick & Elstein 1987, Priddy et al 1990, Jesam et al 2010, 2014. In mares, flunixin meglumine (FM) at a dose rate of 1.7 or 2.0 mg/kg body weight has been shown to induce LUFs in 73-83% of mares respectively , Cuervo-Arango & Domingo-Ortiz 2011.…”

Topical Bromfenac Sodium for Long-Term Management of Vernal Keratoconjunctivitis

“…The reason why bromfenac sodium possesses inhibitory activity in VKC recurrence is unclear from our study. However, it has been reported that systemic bromfenac treatment significantly reduces not only PGE 2 and PGF 2 α levels in the follicular fluid, but also LTB 4 levels compared with those after placebo treatment in humans [25]. The LTB 4 level in tears of patients with VKC is reported to be elevated [26].…”